In recent years, the availability of high resolution crystal structures of enzyme-inhibitor complexes have led to an increased understanding of molecular interactions. Using this structural information, computer-based approaches help identify or design ligands that possess good steric and chemical complementarity to various sites on the enzyme. This process is referred to as "structure-based molecular design". The long-term objective of this work is to develop a method to computationally screen and evaluate ligands as potential lead compounds. We are seeking a method that is both rapid and reasonably accurate. Traditionally, our group has treated both the enzyme and ligand as rigid objects, with only one conformation of the enzyme and ligand considered. We are now attempting to incorporate ligand and receptor flexibility in the screening process. An earlier part of this work concentrated on evaluating and docking conformationally flexible ligands using a genetic algorithm into a rigid protein. Another part of this work concentrates on taking protein flexibility into consideration by incorporating different protein conformations into an evaluation function. Work continues in both areas. MIDAS is used to examine different conformations and orientations of the ligand in one conformations of enzyme as well as examining several different rigid ligands in different conformations of the same enzyme. MIDAS is also use to display and select site points (referred to as DOCK spheres) within the enzyme active site.